Overexpression of insulin-like growth factor-I receptor as a pertinent biomarker for hepatocytes malignant transformation

• Published in: World journal of gastroenterology : WJG 2013-09, Vol.19 (36), p.6084-6092
• Main Authors: Yan, Xiao-Di, Yao, Min, Wang, Li, Zhang, Hai-Jian, Yan, Mei-Juan, Gu, Xing, Shi, Yun, Chen, Jie, Dong, Zhi-Zhen, Yao, Deng-Fu
• Format: Article
• Language: English
• Subjects: 2-Acetylaminofluorene; Animals; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brief; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Hepatocytes - metabolism; Hepatocytes - pathology; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1 - blood; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; RNA, Messenger - metabolism; Up-Regulation
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v19.i36.6084

To investigate the dynamic features of insulin-like growth factor-I receptor (IGF-IR) expression in rat hepatocarcinogenesis, and the relationship between IGF-IR and hepatocytes malignant transformation at mRNA or protein level. Hepatoma models were made by inducing with 2-fluorenylacetamide (2-FAA) on male Sprague-Dawley rats. Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining, the dynamic expressions of liver and serum IGF-IR were quantitatively analyzed by an enzyme-linked immunosorbent assay. The distribution of hepatic IGF-IR was located by immunohistochemistry. The fragments of IGF-IR gene were amplified by reverse transcription-polymerase chain reaction, and confirmed by sequencing. Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration, precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-IR expression. The incidences of liver IGF-IR, IGF-IR mRNA, specific IGF-IR concentration (ng/mg wet liver), and serum IGF-IR level (ng/mL) were 0.0%, 0.0%, 0.63 ± 0.17, and 1.33 ± 0.47 in the control; 50.0%, 61.1%, 0.65 ± 0.2, and 1.51 ± 0.46 in the degeneration; 88.9%, 100%, 0.66 ± 0.14, and 1.92 ± 0.29 in the precancerosis; and 100%, 100%, 0.96 ± 0.09, and 2.43 ± 0.57 in the cancerous group, respectively. IGF-IR expression in the cancerous group was significantly higher (P < 0.01) than that in any of other groups at mRNA or protein level. The closely positive IGF-IR relationship was found between livers and sera (r = 0.91, t = 14.222, P < 0.01), respectively. IGF-IR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation.